scholarly journals Olfactory dysfunction is worse in primary ciliary dyskinesia compared with other causes of chronic sinusitis in children

Thorax ◽  
2018 ◽  
Vol 73 (10) ◽  
pp. 980-982 ◽  
Author(s):  
Massimo Pifferi ◽  
Andrew Bush ◽  
Michele Rizzo ◽  
Alessandro Tonacci ◽  
Maria Di Cicco ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Primary Ciliary Dyskinesia ◽  
Chronic Sinusitis ◽  
Olfactory Dysfunction ◽  
Healthy Controls ◽  
Sinus Disease ◽  
Multiple Functions ◽  
Nasal Nitric Oxide ◽  
Transmission Electron ◽  
Ciliary Dyskinesia

Cilia have multiple functions including olfaction. We hypothesised that olfactory function could be impaired in primary ciliary dyskinesia (PCD). Olfaction, nasal nitric oxide (nNO) and sinus CT were assessed in patients with PCD and non-PCD sinus disease, and healthy controls (no CT scan). PCD and non-PCD patients had similar severity of sinus disease. Despite this, defective olfaction was more common in patients with PCD (P<0.0001) and more severe in patients with PCD with major Transmission Electron Microscopy (TEM) abnormalities. Only in classical PCD did olfaction inversely correlate with sinusitis and nNO. We speculate that defective olfaction in PCD is primary in nature.

scholarly journals Primary ciliary dyskinesia with normal ultrastructure: three-dimensional tomography detects absence of DNAH11

2018 ◽  
Vol 51 (2) ◽  
pp. 1701809 ◽  
Author(s):  
Amelia Shoemark ◽  
Thomas Burgoyne ◽  
Robert Kwan ◽  
Mellisa Dixon ◽  
Mitali P. Patel ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Electron Tomography ◽  
Three Dimensional ◽  
Structural Abnormality ◽  
Healthy Controls ◽  
Ultrastructural Studies ◽  
Transmission Electron ◽  
Causal Variants ◽  
Diagnostic Samples ◽  
Ciliary Dyskinesia

In primary ciliary dyskinesia (PCD), motile ciliary dysfunction arises from ciliary defects usually confirmed by transmission electron microscopy (TEM). In 30% of patients, such as those with DNAH11 mutations, apparently normal ultrastructure makes diagnosis difficult. Genetic analysis supports diagnosis, but may not identify definitive causal variants. Electron tomography, an extension of TEM, produces three-dimensional ultrastructural ciliary models with superior resolution to TEM. Our hypothesis is that tomography using existing patient samples will enable visualisation of DNAH11-associated ultrastructural defects. Dual axis tomograms from araldite-embedded nasal cilia were collected in 13 PCD patients with normal ultrastructure (DNAH11 n=7, HYDIN n=2, CCDC65 n=3 and DRC1 n=1) and six healthy controls, then analysed using IMOD and Chimera software.DNAH11 protein is localised to the proximal ciliary region. Within this region, electron tomography indicated a deficiency of >25% of proximal outer dynein arm volume in all patients with DNAH11 mutations (n=7) compared to other patients with PCD and normal ultrastructure (n=6) and healthy controls (n=6). DNAH11 mutations cause a shared abnormality in ciliary ultrastructure previously undetectable by TEM. Advantageously, electron tomography can be used on existing diagnostic samples and establishes a structural abnormality where ultrastructural studies were previously normal.

scholarly journals Frequency and Types of Ciliary Ultrastructural Defects in Patients With Suspected Primary Ciliary Dyskinesia Symptoms Analyzed by Transmission Electron Microscopy

2021 ◽  
Author(s):  
Mitra Rezaei ◽  
Amirali Soheili ◽  
Atefeh Fakharian ◽  
Hamid Jamaati ◽  
Jahangir Ghorbani ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Primary Ciliary Dyskinesia ◽  
Respiratory Infections ◽  
Descriptive Analysis ◽  
Final Diagnosis ◽  
International Consensus ◽  
Tem Analysis ◽  
Transmission Electron ◽  
Ciliary Dyskinesia

Abstract Background: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive condition of often chronic respiratory infections in early life. A useful tool for early diagnosis of such ciliary abnormalities is transmission electron microscopy (TEM). This study aimed to use TEM to examine these defects and speculate on a diagnosis.Methods: From 2017 to 2019, all referral patients with suspected PCD symptoms were included in this study. Nasal samples were taken after exclusion of further potential differential diagnosis and prepared for TEM. The final diagnosis was based on the International Consensus Guideline for reporting transmission electron microscopy results in the diagnosis of PCD. A descriptive analysis of demographic and ciliary ultrastructural data was performed by SPSS ver 21.Results: Study population consisted of 37 women and 30 men (mean age=20.34±10.7 years). The clinical presentations were as follows: bronchiectasis: 26 patients (38.8%); sinusitis: 23(34.3%); recurrent respiratory infection: 21 patients (31.3%); auditory symptoms: 5 patients (7.5%); situs inversus: 3 patients (4.4%); productive cough: 2 patients (3%); infertility: 2 patients (3%); polyposis: 1 patient (1.5%). According to TEM analysis, 12 (17%) of patients were PCD, 11 (15.7%) were indicating PCD cases, 26 (37.1%) of them had no criteria of PCD and 18 (25.7%) of cases had normal ciliary ultrastructure. Compound cilia and extra-tubule were reported in 29 (41.4%) and 31(44.3%) of patients, respectively. The outer dynein arm defect was seen in 11(16.4%) cases and the inner dynein arm (IDA) defect was seen in 20 (29.8%) cases. Two patients (3%) had microtubular disorganization.Conclusion: Bronchiectasis and sinusitis were the most common complications. The compound cilia and extra-tubule were the most prevalent TEM finding among all participants. However, the most prevalent hallmark diagnostic defects among PCD patients were ODA and IDA defects among PCD patients. Other diagnostic PCD tests should also be performed in patients in the indicating PCD group, those without PCD criteria, and normal patients with a highly suggestive history. Cell-culture, as well, should confirm IDA defects. This study highlights the fundamental need to consider ciliary defect among probable diagnoses and use TEM as a practical diagnostic tool.

scholarly journals Ciliary Feature Counter: A program for the Quantitative Assessment of Cilia to Diagnose Primary Ciliary Dyskinesia

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 524
Author(s):  
Andreia L. Pinto ◽  
Ranjit K. Rai ◽  
Claire Hogg ◽  
Thomas Burgoyne
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Primary Ciliary Dyskinesia ◽  
Quantitative Assessment ◽  
Consensus Guideline ◽  
International Consensus ◽  
Transmission Electron ◽  
Speed Up ◽  
Ciliary Dyskinesia ◽  
Ciliary Ultrastructure

Primary ciliary dyskinesia (PCD) is a disorder that affects motile cilia in the airway that are required for the removal of mucus, debris, and pathogens. It is important to diagnose PCD in early childhood to preserve lung function. The confirmation of a diagnosis relies on the assessment of ciliary ultrastructure by transmission electron microscopy (TEM). TEM involves the quantitative assessment of the ciliary ultrastructure to identify PCD defects as well as abnormalities resulting from infection. Many specialist diagnostic centres still rely on physical counters to tally results and paper notes to summarise findings before transferring the results to computer databases/records. To speed up the diagnostic data collection and increase the protection of patient information, we have developed digital ciliary feature counters that conform to the PCD reporting international consensus guideline. These counters can be used on a computer or tablet, and automatically generate notes regarding sample observations. We show that the digital counters are easy to use and can generate TEM diagnostic reports that will be useful for many PCD diagnostic centres.

scholarly journals Diagnosis of primary ciliary dyskinesia: potential options for resource-limited countries

2017 ◽  
Vol 26 (143) ◽  
pp. 160058 ◽  
Author(s):  
Nisreen Rumman ◽  
Claire Jackson ◽  
Samuel Collins ◽  
Patricia Goggin ◽  
Janice Coles ◽  
...  
Keyword(s):  
Diagnostic Tests ◽  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Care Setting ◽  
Nasal Nitric Oxide ◽  
Ciliary Function ◽  
Resource Limited ◽  
Transmission Electron ◽  
Sophisticated Equipment ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia is a genetic disease of ciliary function leading to chronic upper and lower respiratory tract symptoms. The diagnosis is frequently overlooked because the symptoms are nonspecific and the knowledge about the disease in the primary care setting is poor. Additionally, none of the available tests is accurate enough to be used in isolation. These tests are expensive, and need sophisticated equipment and expertise to analyse and interpret results; diagnosis is therefore only available at highly specialised centres. The diagnosis is particularly challenging in countries with limited resources due to the lack of such costly equipment and expertise.In this review, we discuss the importance of early and accurate diagnosis especially for countries where the disease is clinically prevalent but diagnostic tests are lacking. We review the diagnostic tests available in specialised centres (nasal nitric oxide, high-speed video microscopy, transmission electron microscopy, immunofluorescence and genetics). We then consider modifications that might be considered in less well-resourced countries whilst maintaining acceptable accuracy.

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